Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy
Xiaodan Ren, … , Audra Carpenter, Lisa Colletti
Xiaodan Ren, … , Audra Carpenter, Lisa Colletti
Published November 1, 2003
Citation Information: J Clin Invest. 2003;112(9):1407-1418. https://doi.org/10.1172/JCI17391.
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Article Hepatology

Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy

Abstract

Stem cell factor (SCF) is a molecule with known proliferative effects on hematopoietic cells. More recent studies suggest that this molecule may also have effects on cellular differentiation and proliferation in other types of cells. The current investigations demonstrate that there is a large reservoir of SCF in the liver, that hepatic SCF levels change dramatically following partial hepatectomy in mice, and that SCF blockade, either by administration of anti-SCF antibodies or by using genetically altered, SCF-deficient mice, inhibits hepatocyte proliferation after partial hepatectomy; if SCF is replaced in the genetically SCF-deficient mice after partial hepatectomy, hepatocyte proliferation is restored to that seen in WT animals. Furthermore, SCF administration to IL-6 knockout mice also restores hepatocyte proliferation to normal. In vitro studies using primary mouse hepatocytes demonstrate that SCF causes hepatocyte proliferation and is induced by IL-6 and that treatment with anti-SCF antibodies inhibits IL-6–induced hepatocyte proliferation. Further in vivo studies in IL-6 knockout mice demonstrate that SCF administration to these animals increases p-stat3 levels, suggesting that the SCF-induced increase in hepatocyte proliferation in this system is stat3-mediated.

Authors

Xiaodan Ren, Cory Hogaboam, Audra Carpenter, Lisa Colletti

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Figure 1

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Hepatic and serum SCF levels after partial hepatectomy. Animals underwen...
Hepatic and serum SCF levels after partial hepatectomy. Animals underwent 70% hepatectomy or sham laparotomy and liver tissue and serum was obtained for SCF quantitation by ELISA at various times postoperatively. Hepatic tissue SCF levels were normalized to tissue weight and expressed as ng/mg tissue. Serum SCF levels were expressed as ng/ml. Sham-operated control animals demonstrated high constitutive levels of hepatic SCF, in the range of 2,000–3,000 ng/mg tissue, and low serum SCF content. (a) Following 70% hepatectomy, hepatic SCF levels initially drop, then increase to supranormal levels 24–48 hours after hepatectomy, and then gradually drop to baseline levels. (b) In contrast, following 70% hepatectomy, serum SCF levels initially increase significantly, concurrent with the drop that is seen in hepatic SCF levels, then subsequently gradually decline to baseline levels. This suggests that bound hepatic SCF may be cleaved into the soluble form and released into the systemic circulation in response to hepatectomy. *P < 0.05 vs. sham-operated control animals. Data is expressed as mean ± SEM.